Npas4 overexpression inhibits β-cell responsiveness to the GLP-1 receptor agonist exendin-4. MIN6 cells were transduced with
control (Ad-Cerulean, white bars) or Npas4 (Ad-Npas4, black bars) adenovirus and then cultured for 48 h. No statistical difference
was observed in glucose-stimulated insulin secretion in either MIN6 cells (n = 3–5) (A) or islets (n = 5–6) (B). However, exendin-4–potentiated insulin secretion was reduced after Ad-Npas4 transduction in both MIN6 cells (A) and mouse pancreatic islets (B). Npas4 overexpression diminished exendin-4–stimulated cAMP production in MIN6, significantly reducing maximal stimulation
as well as shifting the EC50 from 0.76 to 2.65 nmol/L (n = 3) (C). Significance was determined using two-tailed Student t tests or a one-way ANOVA with Dunnett post hoc analysis where applicable. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001.